Application of Transcriptome Analysis for the Exploration of the Mechanism of Methionine Promoting the Synthesis of Cephalosporin C in <i>Acremonium chrysogenum</i> by Employing a Chemically Defined Medium
To better analyze the biosynthesis mechanism of cephalosporin C (CPC) in <i>Acremonium chrysogenum</i>, single-factor omission experiments and Plackett–Burman (PB) experimental design were employed to identify key components in the chemically defined medium. Response surface methodology...
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MDPI AG
2025-06-01
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| Series: | Fermentation |
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| Online Access: | https://www.mdpi.com/2311-5637/11/6/325 |
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| author | Yifan Li Zhen Chen Wei Hong Tao Feng Xiwei Tian Ju Chu |
| author_facet | Yifan Li Zhen Chen Wei Hong Tao Feng Xiwei Tian Ju Chu |
| author_sort | Yifan Li |
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| description | To better analyze the biosynthesis mechanism of cephalosporin C (CPC) in <i>Acremonium chrysogenum</i>, single-factor omission experiments and Plackett–Burman (PB) experimental design were employed to identify key components in the chemically defined medium. Response surface methodology (RSM) was then applied to optimize the concentrations of critical factors, achieving a final CPC titer of 4.70 g/L, which reached 59.54% of the titer obtained with complex medium. Methionine was identified as the most significant amino acid influencing CPC production during medium optimization. On the basis of these findings, transcriptomic analysis was conducted to elucidate the regulatory role of methionine. The results revealed that methionine enhances CPC biosynthesis by upregulating cysteine metabolism-related genes and activating primary metabolic pathways to supply precursors and energy for secondary metabolism. Additionally, methionine promoted hyphal swelling and arthrospore formation, leading to the upregulated expression of genes in CPC biosynthetic gene clusters. By integrating medium optimization with transcriptomic analysis, we provided more reliable insights into the regulatory role of methionine in <i>A. chrysogenum</i> growth and CPC biosynthesis using a chemically defined medium, offering valuable guidance for fermentation process optimization and subsequent metabolic engineering strategies. |
| format | Article |
| id | doaj-art-a3c85835c74a4230ac52a04751ecf858 |
| institution | Kabale University |
| issn | 2311-5637 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Fermentation |
| spelling | doaj-art-a3c85835c74a4230ac52a04751ecf8582025-08-20T03:24:33ZengMDPI AGFermentation2311-56372025-06-0111632510.3390/fermentation11060325Application of Transcriptome Analysis for the Exploration of the Mechanism of Methionine Promoting the Synthesis of Cephalosporin C in <i>Acremonium chrysogenum</i> by Employing a Chemically Defined MediumYifan Li0Zhen Chen1Wei Hong2Tao Feng3Xiwei Tian4Ju Chu5State Key Laboratory of Bioreactor Engineering, Qingdao Innovation Institute, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Qingdao Innovation Institute, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Qingdao Innovation Institute, East China University of Science and Technology, Shanghai 200237, ChinaSinopharm Weiqida Pharmaceutical Co., Ltd., Datong 037000, ChinaState Key Laboratory of Bioreactor Engineering, Qingdao Innovation Institute, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Qingdao Innovation Institute, East China University of Science and Technology, Shanghai 200237, ChinaTo better analyze the biosynthesis mechanism of cephalosporin C (CPC) in <i>Acremonium chrysogenum</i>, single-factor omission experiments and Plackett–Burman (PB) experimental design were employed to identify key components in the chemically defined medium. Response surface methodology (RSM) was then applied to optimize the concentrations of critical factors, achieving a final CPC titer of 4.70 g/L, which reached 59.54% of the titer obtained with complex medium. Methionine was identified as the most significant amino acid influencing CPC production during medium optimization. On the basis of these findings, transcriptomic analysis was conducted to elucidate the regulatory role of methionine. The results revealed that methionine enhances CPC biosynthesis by upregulating cysteine metabolism-related genes and activating primary metabolic pathways to supply precursors and energy for secondary metabolism. Additionally, methionine promoted hyphal swelling and arthrospore formation, leading to the upregulated expression of genes in CPC biosynthetic gene clusters. By integrating medium optimization with transcriptomic analysis, we provided more reliable insights into the regulatory role of methionine in <i>A. chrysogenum</i> growth and CPC biosynthesis using a chemically defined medium, offering valuable guidance for fermentation process optimization and subsequent metabolic engineering strategies.https://www.mdpi.com/2311-5637/11/6/325Cephalosporin Cchemically defined mediummethioninetranscriptomics |
| spellingShingle | Yifan Li Zhen Chen Wei Hong Tao Feng Xiwei Tian Ju Chu Application of Transcriptome Analysis for the Exploration of the Mechanism of Methionine Promoting the Synthesis of Cephalosporin C in <i>Acremonium chrysogenum</i> by Employing a Chemically Defined Medium Fermentation Cephalosporin C chemically defined medium methionine transcriptomics |
| title | Application of Transcriptome Analysis for the Exploration of the Mechanism of Methionine Promoting the Synthesis of Cephalosporin C in <i>Acremonium chrysogenum</i> by Employing a Chemically Defined Medium |
| title_full | Application of Transcriptome Analysis for the Exploration of the Mechanism of Methionine Promoting the Synthesis of Cephalosporin C in <i>Acremonium chrysogenum</i> by Employing a Chemically Defined Medium |
| title_fullStr | Application of Transcriptome Analysis for the Exploration of the Mechanism of Methionine Promoting the Synthesis of Cephalosporin C in <i>Acremonium chrysogenum</i> by Employing a Chemically Defined Medium |
| title_full_unstemmed | Application of Transcriptome Analysis for the Exploration of the Mechanism of Methionine Promoting the Synthesis of Cephalosporin C in <i>Acremonium chrysogenum</i> by Employing a Chemically Defined Medium |
| title_short | Application of Transcriptome Analysis for the Exploration of the Mechanism of Methionine Promoting the Synthesis of Cephalosporin C in <i>Acremonium chrysogenum</i> by Employing a Chemically Defined Medium |
| title_sort | application of transcriptome analysis for the exploration of the mechanism of methionine promoting the synthesis of cephalosporin c in i acremonium chrysogenum i by employing a chemically defined medium |
| topic | Cephalosporin C chemically defined medium methionine transcriptomics |
| url | https://www.mdpi.com/2311-5637/11/6/325 |
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